Inhibition of human islet amyloid polypeptide aggregation and cellular toxicity by oleuropein and derivatives from olive oil

Abstract

AbstractBackgroundBeta‐cell death is the key feature of type 2 diabetes mellitus (T2DM). One hypothesis for the mechanism of this feature is amyloid formation by the human Islet Amyloid Polypeptide (hIAPP). Clinical trials and population studies indicate the healthy virtues of the Mediterranean diet, especially the extra virgin olive oil (EVOO) found in this diet. This oil is enriched in phenolic compounds shown to be effective against several aging and lifestyle diseases. Oleuropein (Ole), one of the most abundant polyphenols in EVOO, has been reported to be anti‐diabetic.MethodI report here a broad biophysical approach and cell biology techniques that enabled me to characterize the different molecular mechanisms by which tyrosol (TYR), hydroxytyrosol (HT), oleuropein (Ole) and oleuropein aglycone (OleA) modulate the hIAPP fibrillation in vitro and their effects on cell cytotoxicity.ResultOleA was found to be more active than Ole, HT and TYR at low micromolar concentrations. I further demonstrated that comparing to other used polyphenols, OleA inhibits the cytotoxicity induced by hIAPP aggregates by protecting more the cell membrane from permeabilization and then from death.ConclusionThese findings highlight the benefits of consuming EVOO and the great potential of its polyphenols. Moreover, they support the possible pharmacological use of EVOO polyphenols for T2DM prevention and therapy as well as for many other amyloid‐related diseases.